PMID- 28492279 OWN - NLM STAT- MEDLINE DCOM- 20180730 LR - 20221207 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 42 IP - 13 DP - 2017 Dec TI - Dose-Related Effects of Adjunctive Ketamine in Taiwanese Patients with Treatment-Resistant Depression. PG - 2482-2492 LID - 10.1038/npp.2017.94 [doi] AB - The antidepressant effects of ketamine are thought to depend on brain-derived neurotrophic factor (BDNF) genotype and dose. The purpose of this study was to characterize the dose-related antidepressant effects of ketamine in patients with treatment-resistant depression drawn from a Chinese population predominately possessing lower activity BDNF genotypes (Val/Met, Met/Met). We conducted a double-blind, randomized, parallel-group, placebo-controlled trial of a single ketamine infusion (saline, 0.2 mg/kg, 0.5 mg/kg). Patients (N=71; BDNF genotype: Val/Val (N=12, 17%), Val/Met (N=40, 56.3%), and Met/Met (N=19, 26.8%)) received mood ratings before infusion, after infusion, and for the subsequent 14 days. Plasma ketamine levels and BDNF genotypes were assessed. This study found a significant dose-related ketamine effect on scores on the Hamilton Depression Rating Scale (HAMD). The responder analysis (>50% reduction from baseline HAMD on at least 2 days between days 2 and 5) also revealed a significant dose-related effect (saline: 12.5%, 0.2 mg/kg: 39.1%; 0.5 mg/kg: 45.8%). This is the first report to our knowledge to demonstrate the dose-related efficacy of R/S-ketamine for treatment-resistant depression and the first to characterize ketamine effects in a genotyped Chinese population in which most (83%) patients possessed at least one copy of the lower functioning Met allele of the BDNF gene. FAU - Su, Tung-Ping AU - Su TP AD - Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. FAU - Chen, Mu-Hong AU - Chen MH AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. FAU - Li, Cheng-Ta AU - Li CT AD - Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. FAU - Lin, Wei-Chen AU - Lin WC AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. FAU - Hong, Chen-Jee AU - Hong CJ AD - Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. FAU - Gueorguieva, Ralitza AU - Gueorguieva R AD - Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, USA. AD - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. FAU - Tu, Pei-Chi AU - Tu PC AD - Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. AD - Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Bai, Ya-Mei AU - Bai YM AD - Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan. AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Cheng, Chih-Ming AU - Cheng CM AUID- ORCID: 0000-0001-8334-0438 AD - Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan. FAU - Krystal, John H AU - Krystal JH AD - Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. AD - Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA. AD - Yale-New Haven Hospital, New Haven, CT, USA. AD - VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA. LA - eng GR - M01 RR000125/RR/NCRR NIH HHS/United States GR - P50 AA012870/AA/NIAAA NIH HHS/United States GR - UL1 RR024139/RR/NCRR NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial DEP - 20170511 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 690G0D6V8H (Ketamine) RN - 7171WSG8A2 (BDNF protein, human) RN - XQY6JVF94X (norketamine) SB - IM EIN - Neuropsychopharmacology. 2019 Feb;44(3):655-656. PMID: 30487654 MH - Adult MH - Antidepressive Agents/*administration & dosage/blood MH - Asian People/genetics MH - Blood Pressure/drug effects MH - Brain-Derived Neurotrophic Factor/genetics MH - Depressive Disorder, Major/blood/*drug therapy/genetics MH - Depressive Disorder, Treatment-Resistant/blood/*drug therapy/genetics MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Heart Rate/drug effects MH - Humans MH - Ketamine/*administration & dosage/analogs & derivatives/blood MH - Male MH - Middle Aged MH - Polymorphism, Genetic MH - Psychiatric Status Rating Scales MH - Taiwan MH - Treatment Outcome PMC - PMC5686503 EDAT- 2017/05/12 06:00 MHDA- 2018/07/31 06:00 PMCR- 2018/12/01 CRDT- 2017/05/12 06:00 PHST- 2017/01/13 00:00 [received] PHST- 2017/03/30 00:00 [revised] PHST- 2017/04/30 00:00 [accepted] PHST- 2017/05/12 06:00 [pubmed] PHST- 2018/07/31 06:00 [medline] PHST- 2017/05/12 06:00 [entrez] PHST- 2018/12/01 00:00 [pmc-release] AID - npp201794 [pii] AID - 10.1038/npp.2017.94 [doi] PST - ppublish SO - Neuropsychopharmacology. 2017 Dec;42(13):2482-2492. doi: 10.1038/npp.2017.94. Epub 2017 May 11.